alpha-Ketoacids scavenge H2O2 in vitro and in vivo and reduce menadione-induced DNA injury and cytotoxicity.
摘要:
We demonstrate that alpha-ketoacids reduce and, in some instances, abrogate -induced DNA damage and cytotoxicity in the breast line, MCF7. We confirm that alpha-ketoacids quench the copious amounts of H2O2 generated by while these alpha-ketoacids undergo nonenzymatic oxidative decarboxylation; our data thus support enhanced H2O2 production as an important pathway for -induced DNA damage and cytotoxicity. We also demonstrate that alpha-ketoacids scavenge H2O2 generated by and microsomes when these are exposed to ; additionally, alpha-ketoacids protect oxidant-vulnerable enzymes against functional impairment induced by H2O2. Finally, we provide the first in vivo demonstration that acute elevations in concentrations of alpha-ketoacids in tissues and urine scavenge H2O2. We conclude that enhanced H2O2 production is a major pathway for -induced DNA damage and cytotoxicity and that the diverse alpha-ketoacids present within the must be considered, along with and , as part of the antioxidant defense mechanisms that regulate the ambient levels of H2O2.
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DOI:
10.1016/S0065-2776(08)60589-1
被引量:
年份:
1995
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